A Study to Test Whether Different Doses of BI 456906 Are... | NCT04153929

ID	Type	Description	Link
2019-002390-60	EudraCT Number

Label	Type	Intervention Names
BI 456906 0.3 mg	Experimental	Drug: BI 456906
BI 456906 0.9 mg	Experimental	Drug: BI 456906
BI 456906 1.8 mg	Experimental	Drug: BI 456906
BI 456906 2.7 mg	Experimental	Drug: BI 456906
BI 456906 1.2 twice weekly (2.4) mg	Experimental	Drug: BI 456906
BI 456906 1.8 twice weekly (3.6) mg	Experimental	Drug: BI 456906
Semaglutide	Active Comparator	Drug: Semaglutide
Placebo	Placebo Comparator

Name	Type	Description	Arm Group Labels	Other Names
BI 456906	Drug	Solution for Injection	BI 456906 0.3 mg BI 456906 0.9 mg BI 456906 1.2 twice weekly (2.4) mg BI 456906 1.8 mg

Measure	Description	Time Frame
Absolute Change in HbA1c From Baseline to 16 Weeks	Absolute change in glycosylated hemoglobin A1c (HbA1c) from baseline to 16 weeks after treatment start is presented. The measurements for this outcome were performed at baseline and at Week 17. Absolute change from baseline in HbA1c to 16 weeks after treatment start was calculated by subtracting the baseline HbA1c value from the HbA1c value at Week 17.	At baseline and at Week 17 (16 weeks after treatment start).

Measure	Description	Time Frame
Key Secondary Endpoint: The Relative Change in Body Weight From Baseline to 16 Weeks	The relative change in body weight from baseline to 16 weeks after treatment start is presented. The measurements for this outcome were performed at baseline and at Week 17. The relative change in body weight from baseline to 16 weeks after treatment start was calculated as (body weight at Week 17 - body weight at baseline/body weight at baseline) * 100.

Eligibility Module

Eligibility Criteria

Inclusion criteria:

Signed and dated written informed consent in accordance with International conference on harmonization - Good clinical practice (ICH GCP) and local legislation.
Male and female patients 18 years to 75 years (both inclusive) of age on the day of signing informed consent.
Diagnosis of Type 2 diabetes mellitus (T2DM) at least 6 months prior to informed consent.
Glycosylated hemoglobin A1c (HbA1c) 7.0%-10.0% (both inclusive) at screening.
Treatment with a stable dose of metformin ≥ 1000mg/day for at least 3 months prior to screening.
Body mass index (BMI) 25 kg/m2-50 kg/m2 (both inclusive) at screening.
Women of childbearing potential must be ready and able to use highly effective methods of birth control.

Exclusion criteria:

Patients with type 1 diabetes.
Exposure to semaglutide, or other Glucagon-like-peptide 1 receptor (GLP-1R) agonists (including combination products) within 3 months prior to screening, or any previous exposure to BI 456906.
Any additional oral anti-hyperglycemic medication beyond metformin within 3 months prior to screening.
Use of insulin for glycemic control within 12 months prior to screening.
Resting Heart Rate >100 bpm or blood pressure ≥160/95 mmHg at screening.
A marked baseline prolongation of QT/QTc (Fridericia) interval or any other clinically significant Electrocardiogram (ECG) finding at screening.
Body weight change of +/- 5% or more in the past 3 months or on anti-obesity therapies at any time during the 6 months prior to screening.
Continuous oral pharmacotherapy to treat any clinical condition during the Trial. Following medications are allowed:
- metformin, anti-hypertensives (any medication known to cause heart block or bradycardia such as beta-blockers, verapamil and diltiazem are excluded unless used to treat heart rate control or hypertension),
- Hormone replacement therapy including thyroid hormone, lipid lowering, proton pump inhibitors, H2 blockers for Gastric esophageal reflux disease (GERD), analgesics,
- sleep medications
- antihistamines
- selective Alpha receptor blocker for benign prostatic hyperplasia Patients must be on a stable dose for at least 3 months Prior to Screening
Any suicidal behavior in the past 2 years, any suicidal ideation of type 4 or 5 in the Columbia-suicide severity rating scale (C-SSRS) in the past 3 months at screening.
Chronic or relevant acute infections.
Women who are pregnant, nursing, or who plan to become pregnant while in the trial.
Further exclusion criteria apply.

Facility	Status	City	State	ZIP	Country	Contacts
National Research Institute		Huntington Park	California	90255	United States
National Research Institute

PubMed Identifier	Type	Citation	Retractions
42331726	Derived	Ekinci EI, Maldonado SG, Unseld A, Martinez JA, Hennige AM, Schoelch C. Dual Glucagon and GLP-1 Receptor Agonist Survodutide Improves Biomarkers of Beta-Cell Function and Insulin Sensitivity in People With Type 2 Diabetes or Living With Overweight/Obesity. Diabetes Obes Metab. 2026 Jun 22. doi: 10.1111/dom.70861. Online ahead of print.
38095657

Label	URL
Related Info	View source

ID	Title	Description
FG000	Placebo	This arm comprises all placebo treated patients, regardless of the dose group in which they were treated. Patients with type 2 diabetes mellitus with insufficient glycaemic control despite diet, exercise and metformin treatment were administered solution for subcutaneous injection of placebo matched to BI 456906 once weekly for 16 weeks or twice weekly for 16 weeks.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Sep 28, 2020	Oct 27, 2022

Arm/Group Information

ID	Title	Description
BG000	Placebo	This arm comprises all placebo treated patients, regardless of the dose group in which they were treated. Patients with type 2 diabetes mellitus with insufficient glycaemic control despite diet, exercise and metformin treatment were administered solution for subcutaneous injection of placebo matched to BI 456906 once weekly for 16 weeks or twice weekly for 16 weeks.
BG001	BI 456906 0.3 mg	Patients with type 2 diabetes mellitus with insufficient glycaemic control despite diet, exercise and metformin treatment were administered once weekly subcutaneously a solution for injection of BI 456906 of 0.3 milligram (mg) on Week 1-Week 16.
BG002	BI 456906 0.9 mg	Patients with type 2 diabetes mellitus with insufficient glycaemic control despite diet, exercise and metformin treatment were administered once weekly subcutaneously a solution for injection of BI 456906 of 0.3 milligram (mg) on Week 1 and Week 2, 0.6 mg on Week 3 and Week 4, 0.9 mg on Week 5-Week 16.
BG003	BI 456906 1.8 mg	Patients with type 2 diabetes mellitus with insufficient glycaemic control despite diet, exercise and metformin treatment were administered once weekly subcutaneously a solution for injection of BI 456906 of 0.3 milligram (mg) on Week 1, 0.6 mg on Week 2, 0.9 mg on Week 3, 1.2 mg on Week 4, 1.5 mg on Week 5, and 1.8 mg on Week 6- Week 16.
BG004	BI 456906 2.7 mg	Patients with type 2 diabetes mellitus with insufficient glycaemic control despite diet, exercise and metformin treatment were administered once weekly subcutaneously a solution for injection of BI 456906 of 0.6 milligram (mg) on Week 1 and Week 2, 1.2 mg on Week 3 and Week 4, 1.8 mg on Week 5, 2.4 mg on Week 6, 2.7 mg on Week 7- Week 16.
BG005	BI 456906 1.2 Twice Weekly (2.4) mg	Patients with type 2 diabetes mellitus with insufficient glycaemic control despite diet, exercise and metformin treatment were administered twice weekly subcutaneously a solution for injection of BI 456906 of 0.3 milligram (mg) on Week 1 and Week 2 (total weekly dose=0.6 mg), 0.6 mg on Week 3 and Week 4 (total weekly dose=1.2 mg), 0.9 mg on Week 5 and Week 6 (total weekly dose=1.8 mg), 1.2 mg on Week 7- Week 16 (total weekly dose 2.4 mg).
BG006	BI 456906 1.8 Twice Weekly (3.6) mg	Patients with type 2 diabetes mellitus with insufficient glycaemic control despite diet, exercise and metformin treatment were administered twice weekly subcutaneously a solution for injection of BI 456906 of 0.3 milligram (mg) on Week 1 (total weekly dose=0.6 mg), 0.6 mg on Week 2 (total weekly dose=1.2 mg), 0.9 mg on Week 3 (total weekly dose=1.8 mg), 1.2 mg on Week 4 (total weekly dose 2.4 mg), 1.5 mg on Week 5 and on Week 6 (total weekly dose 3 mg), 1.8 mg on Week 7 -Week 16 (total weekly dose =3.6 mg).
BG007	Semaglutide	Patients with type 2 diabetes mellitus with insufficient glycaemic control despite diet, exercise and metformin treatment were administered once weekly subcutaneously a solution for injection of Semaglutide of 0.25 milligram (mg) on Week 1-Week 4, 0.5 mg on Week 5-Week 8, 1.0 mg on Week 9-Week 16.
BG008	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Absolute Change in HbA1c From Baseline to 16 Weeks

Absolute change in glycosylated hemoglobin A1c (HbA1c) from baseline to 16 weeks after treatment start is presented. The measurements for this outcome were performed at baseline and at Week 17.

Absolute change from baseline in HbA1c to 16 weeks after treatment start was calculated by subtracting the baseline HbA1c value from the HbA1c value at Week 17.

Full Analysis Set (FAS): This patient set included all patients who were randomized and received at least one dose of study drug and who had analysable data for at least one efficacy endpoint. Only patients with non-missing results are reported.

Posted

Mean

Standard Deviation

percentage (%) of HbA1c

At baseline and at Week 17 (16 weeks after treatment start).

ID	Title	Description
OG000	Placebo	This arm comprises all placebo treated patients, regardless of the dose group in which they were treated. Patients with type 2 diabetes mellitus with insufficient glycaemic control despite diet, exercise and metformin treatment were administered solution for subcutaneous injection of placebo matched to BI 456906 once weekly for 16 weeks or twice weekly for 16 weeks.
OG001	BI 456906 0.3 mg	Patients with type 2 diabetes mellitus with insufficient glycaemic control despite diet, exercise and metformin treatment were administered once weekly subcutaneously a solution for injection of BI 456906 of 0.3 milligram (mg) on Week 1-Week 16.
OG002	BI 456906 0.9 mg	Patients with type 2 diabetes mellitus with insufficient glycaemic control despite diet, exercise and metformin treatment were administered once weekly subcutaneously a solution for injection of BI 456906 of 0.3 milligram (mg) on Week 1 and Week 2, 0.6 mg on Week 3 and Week 4, 0.9 mg on Week 5-Week 16.
OG003	BI 456906 1.8 mg	Patients with type 2 diabetes mellitus with insufficient glycaemic control despite diet, exercise and metformin treatment were administered once weekly subcutaneously a solution for injection of BI 456906 of 0.3 milligram (mg) on Week 1, 0.6 mg on Week 2, 0.9 mg on Week 3, 1.2 mg on Week 4, 1.5 mg on Week 5, and 1.8 mg on Week 6- Week 16.
OG004	BI 456906 2.7 mg	Patients with type 2 diabetes mellitus with insufficient glycaemic control despite diet, exercise and metformin treatment were administered once weekly subcutaneously a solution for injection of BI 456906 of 0.6 milligram (mg) on Week 1 and Week 2, 1.2 mg on Week 3 and Week 4, 1.8 mg on Week 5, 2.4 mg on Week 6, 2.7 mg on Week 7- Week 16.
OG005	BI 456906 1.2 Twice Weekly (2.4) mg	Patients with type 2 diabetes mellitus with insufficient glycaemic control despite diet, exercise and metformin treatment were administered twice weekly subcutaneously a solution for injection of BI 456906 of 0.3 milligram (mg) on Week 1 and Week 2 (total weekly dose=0.6 mg), 0.6 mg on Week 3 and Week 4 (total weekly dose=1.2 mg), 0.9 mg on Week 5 and Week 6 (total weekly dose=1.8 mg), 1.2 mg on Week 7- Week 16 (total weekly dose 2.4 mg).
OG006	BI 456906 1.8 Twice Weekly (3.6) mg	Patients with type 2 diabetes mellitus with insufficient glycaemic control despite diet, exercise and metformin treatment were administered twice weekly subcutaneously a solution for injection of BI 456906 of 0.3 milligram (mg) on Week 1 (total weekly dose=0.6 mg), 0.6 mg on Week 2 (total weekly dose=1.2 mg), 0.9 mg on Week 3 (total weekly dose=1.8 mg), 1.2 mg on Week 4 (total weekly dose 2.4 mg), 1.5 mg on Week 5 and on Week 6 (total weekly dose 3 mg), 1.8 mg on Week 7 -Week 16 (total weekly dose =3.6 mg).
OG007	Semaglutide	Patients with type 2 diabetes mellitus with insufficient glycaemic control despite diet, exercise and metformin treatment were administered once weekly subcutaneously a solution for injection of Semaglutide of 0.25 milligram (mg) on Week 1-Week 4, 0.5 mg on Week 5-Week 8, 1.0 mg on Week 9-Week 16.

Units	Counts
Participants	OG00049 OG00141 OG00246 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-0.23± 0.81 OG001-0.91± 0.71 OG002-1.37± 0.93 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001 OG002 OG003 OG004 OG005 OG006	A flat vs. non-flat dose-response relationship across the 6 doses of BI 456906 and placebo was tested using the Multiple Comparison Procedure - Modelling (MCP-Mod) approach which evaluated simultaneously 5 different plausible dose-response patterns (linear, exponential, Emax 1, Emax 2 and Sigmoid Emax) while protecting the overall probability of type I error (one-sided alpha of 0.025). For the twice weekly dosing schemes the total dose per week was considered for the MCP-Mod analysis.	MCP-Mod linear model fit	Model assumption: The maximum effect is achieved at 3.6 mg dose.	<0.0001

Secondary

Key Secondary Endpoint: The Relative Change in Body Weight From Baseline to 16 Weeks

The relative change in body weight from baseline to 16 weeks after treatment start is presented. The measurements for this outcome were performed at baseline and at Week 17.

The relative change in body weight from baseline to 16 weeks after treatment start was calculated as (body weight at Week 17 - body weight at baseline/body weight at baseline) * 100.

Posted

Mean

Standard Deviation

percentage of body weight change

At baseline and at Week 17 (16 weeks after treatment start ).

ID	Title	Description
OG000	Placebo	This arm comprises all placebo treated patients, regardless of the dose group in which they were treated. Patients with type 2 diabetes mellitus with insufficient glycaemic control despite diet, exercise and metformin treatment were administered solution for subcutaneous injection of placebo matched to BI 456906 once weekly for 16 weeks or twice weekly for 16 weeks.
OG001	BI 456906 0.3 mg	Patients with type 2 diabetes mellitus with insufficient glycaemic control despite diet, exercise and metformin treatment were administered once weekly subcutaneously a solution for injection of BI 456906 of 0.3 milligram (mg) on Week 1-Week 16.

Secondary

The Absolute Change in Body Weight From Baseline to 16 Weeks

The absolute change in body weight from baseline to 16 weeks after treatment start is presented. Measurements for this outcome were performed at baseline and at Week 17.

The absolute change in body weight from baseline to 16 weeks after treatment start was calculated as: body weight at Week 17- body weight at baseline.

Posted

Mean

Standard Deviation

kilogram (kg)

At baseline and at Week 17 (16 weeks after treatment start).

ID	Title	Description
OG000	Placebo	This arm comprises all placebo treated patients, regardless of the dose group in which they were treated. Patients with type 2 diabetes mellitus with insufficient glycaemic control despite diet, exercise and metformin treatment were administered solution for subcutaneous injection of placebo matched to BI 456906 once weekly for 16 weeks or twice weekly for 16 weeks.
OG001	BI 456906 0.3 mg	Patients with type 2 diabetes mellitus with insufficient glycaemic control despite diet, exercise and metformin treatment were administered once weekly subcutaneously a solution for injection of BI 456906 of 0.3 milligram (mg) on Week 1-Week 16.

Secondary

The Absolute Change in Waist Circumference From Baseline to 16 Weeks

The absolute change in waist circumference from baseline to 16 weeks after treatment start is presented. Measurements for this outcome were performed at baseline and at Week 17.

The absolute change in waist circumference from baseline to 16 weeks after treatment start was calculated as: waist circumference at Week 17- waist circumference at baseline.

Posted

Mean

Standard Deviation

centimeter

At baseline and at Week 17 (16 weeks after treatment start).

ID	Title	Description
OG000	Placebo	This arm comprises all placebo treated patients, regardless of the dose group in which they were treated. Patients with type 2 diabetes mellitus with insufficient glycaemic control despite diet, exercise and metformin treatment were administered solution for subcutaneous injection of placebo matched to BI 456906 once weekly for 16 weeks or twice weekly for 16 weeks.
OG001	BI 456906 0.3 mg	Patients with type 2 diabetes mellitus with insufficient glycaemic control despite diet, exercise and metformin treatment were administered once weekly subcutaneously a solution for injection of BI 456906 of 0.3 milligram (mg) on Week 1-Week 16.

Secondary

Percentage of Patients With 5 % or Greater Body Weight Loss From Baseline to 16 Weeks

The percentage of patients with 5 percent (%) or greater body weight loss from baseline to 16 weeks after treatment start is presented.

Measurements for this outcome were performed at baseline and at Week 17.

Posted

Number

percentage of patients

At baseline and at Week 17 (16 weeks after treatment start).

ID	Title	Description
OG000	Placebo	This arm comprises all placebo treated patients, regardless of the dose group in which they were treated. Patients with type 2 diabetes mellitus with insufficient glycaemic control despite diet, exercise and metformin treatment were administered solution for subcutaneous injection of placebo matched to BI 456906 once weekly for 16 weeks or twice weekly for 16 weeks.
OG001	BI 456906 0.3 mg	Patients with type 2 diabetes mellitus with insufficient glycaemic control despite diet, exercise and metformin treatment were administered once weekly subcutaneously a solution for injection of BI 456906 of 0.3 milligram (mg) on Week 1-Week 16.
OG002

Secondary

Percentage of Patients With 10% or Greater Body Weight Loss From Baseline to 16 Weeks

The percentage of patients with 10 % or greater body weight loss from baseline to 16 weeks after treatment start is presented.

Measurements for this outcome were performed at baseline and at Week 17.

Posted

Number

percentage of patients

At baseline and at Week 17 (16 weeks after treatment start).

ID	Title	Description
OG000	Placebo	This arm comprises all placebo treated patients, regardless of the dose group in which they were treated. Patients with type 2 diabetes mellitus with insufficient glycaemic control despite diet, exercise and metformin treatment were administered solution for subcutaneous injection of placebo matched to BI 456906 once weekly for 16 weeks or twice weekly for 16 weeks.
OG001	BI 456906 0.3 mg	Patients with type 2 diabetes mellitus with insufficient glycaemic control despite diet, exercise and metformin treatment were administered once weekly subcutaneously a solution for injection of BI 456906 of 0.3 milligram (mg) on Week 1-Week 16.
OG002

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	This arm comprises all placebo treated patients, regardless of the dose group in which they were treated. Patients with type 2 diabetes mellitus with insufficient glycaemic control despite diet, exercise and metformin treatment were administered solution for subcutaneous injection of placebo matched to BI 456906 once weekly for 16 weeks or twice weekly for 16 weeks.	59	3	59	18	59
EG001	BI 456906 0.3 mg	Patients with type 2 diabetes mellitus with insufficient glycaemic control despite diet, exercise and metformin treatment were administered once weekly subcutaneously a solution for injection of BI 456906 of 0.3 milligram (mg) on Week 1-Week 16.	50	1	50	27	50
EG002	BI 456906 0.9 mg	Patients with type 2 diabetes mellitus with insufficient glycaemic control despite diet, exercise and metformin treatment were administered once weekly subcutaneously a solution for injection of BI 456906 of 0.3 milligram (mg) on Week 1 and Week 2, 0.6 mg on Week 3 and Week 4, 0.9 mg on Week 5-Week 16.	50	4	50	30	50
EG003	BI 456906 1.8 mg	Patients with type 2 diabetes mellitus with insufficient glycaemic control despite diet, exercise and metformin treatment were administered once weekly subcutaneously a solution for injection of BI 456906 of 0.3 milligram (mg) on Week 1, 0.6 mg on Week 2, 0.9 mg on Week 3, 1.2 mg on Week 4, 1.5 mg on Week 5, and 1.8 mg on Week 6- Week 16.	52	3	52	40	52
EG004	BI 456906 2.7 mg	Patients with type 2 diabetes mellitus with insufficient glycaemic control despite diet, exercise and metformin treatment were administered once weekly subcutaneously a solution for injection of BI 456906 of 0.6 milligram (mg) on Week 1 and Week 2, 1.2 mg on Week 3 and Week 4, 1.8 mg on Week 5, 2.4 mg on Week 6, 2.7 mg on Week 7- Week 16.	50	2	50	33	50
EG005	BI 456906 1.2 Twice Weekly (2.4) mg	Patients with type 2 diabetes mellitus with insufficient glycaemic control despite diet, exercise and metformin treatment were administered twice weekly subcutaneously a solution for injection of BI 456906 of 0.3 milligram (mg) on Week 1 and Week 2 (total weekly dose=0.6 mg), 0.6 mg on Week 3 and Week 4 (total weekly dose=1.2 mg), 0.9 mg on Week 5 and Week 6 (total weekly dose=1.8 mg), 1.2 mg on Week 7- Week 16 (total weekly dose 2.4 mg).	51	1	51	33	51
EG006	BI 456906 1.8 Twice Weekly (3.6) mg	Patients with type 2 diabetes mellitus with insufficient glycaemic control despite diet, exercise and metformin treatment were administered twice weekly subcutaneously a solution for injection of BI 456906 of 0.3 milligram (mg) on Week 1 (total weekly dose=0.6 mg), 0.6 mg on Week 2 (total weekly dose=1.2 mg), 0.9 mg on Week 3 (total weekly dose=1.8 mg), 1.2 mg on Week 4 (total weekly dose 2.4 mg), 1.5 mg on Week 5 and on Week 6 (total weekly dose 3 mg), 1.8 mg on Week 7 -Week 16 (total weekly dose =3.6 mg).	49	0	49	37	49
EG007	Semaglutide	Patients with type 2 diabetes mellitus with insufficient glycaemic control despite diet, exercise and metformin treatment were administered once weekly subcutaneously a solution for injection of Semaglutide of 0.25 milligram (mg) on Week 1-Week 4, 0.5 mg on Week 5-Week 8, 1.0 mg on Week 9-Week 16.	50	0	50	20	50

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected50 at risk EG0020 affected50 at risk EG0030 affected52 at risk EG0040 affected50 at risk EG0050 affected51 at risk EG0060 affected49 at risk EG0070 affected50 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected59 at risk EG0010 affected50 at risk EG0020 affected50 at risk EG003
Inguinal hernia	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected50 at risk EG0020 affected50 at risk EG003
Irritable bowel syndrome	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected59 at risk EG0010 affected50 at risk EG0021 affected50 at risk EG003
Mouth ulceration	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected59 at risk EG0010 affected50 at risk EG0021 affected50 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected50 at risk EG0020 affected50 at risk EG003
Cholecystitis	Hepatobiliary disorders	MedDRA 24.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected50 at risk EG0020 affected50 at risk EG003
Autoimmune disorder	Immune system disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected59 at risk EG0010 affected50 at risk EG0021 affected50 at risk EG003
Cellulitis	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 affected59 at risk EG0010 affected50 at risk EG0022 affected50 at risk EG003
Viraemia	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 affected59 at risk EG0010 affected50 at risk EG0020 affected50 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected59 at risk EG0010 affected50 at risk EG0020 affected50 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected59 at risk EG0010 affected50 at risk EG0020 affected50 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected59 at risk EG0010 affected50 at risk EG0020 affected50 at risk EG003
IIIrd nerve paralysis	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected59 at risk EG0010 affected50 at risk EG0020 affected50 at risk EG003
Paraparesis	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected59 at risk EG0010 affected50 at risk EG0020 affected50 at risk EG003
Pharyngeal ulceration	Respiratory, thoracic and mediastinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected59 at risk EG0010 affected50 at risk EG0021 affected50 at risk EG003
Hypotension	Vascular disorders	MedDRA 24.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected50 at risk EG0020 affected50 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal discomfort	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected59 at risk EG0010 affected50 at risk EG0020 affected50 at risk EG0034 affected52 at risk EG0040 affected50 at risk EG0051 affected51 at risk EG0062 affected49 at risk EG0070 affected50 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0002 affected59 at risk EG0013 affected50 at risk EG0021 affected50 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0001 affected59 at risk EG0013 affected50 at risk EG0021 affected50 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected59 at risk EG0013 affected50 at risk EG0022 affected50 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0007 affected59 at risk EG00112 affected50 at risk EG0028 affected50 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected59 at risk EG0014 affected50 at risk EG0023 affected50 at risk EG003
Eructation	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected59 at risk EG0012 affected50 at risk EG0022 affected50 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0001 affected59 at risk EG0012 affected50 at risk EG0023 affected50 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected50 at risk EG0023 affected50 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0005 affected59 at risk EG00110 affected50 at risk EG00214 affected50 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0003 affected59 at risk EG0017 affected50 at risk EG0029 affected50 at risk EG003
Asthenia	General disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected50 at risk EG0022 affected50 at risk EG003
Fatigue	General disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected59 at risk EG0013 affected50 at risk EG0021 affected50 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0003 affected59 at risk EG0010 affected50 at risk EG0022 affected50 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0001 affected59 at risk EG0010 affected50 at risk EG0021 affected50 at risk EG003
Lipase increased	Investigations	MedDRA 24.1	Systematic Assessment	EG0000 affected59 at risk EG0012 affected50 at risk EG0024 affected50 at risk EG003
Weight decreased	Investigations	MedDRA 24.1	Systematic Assessment	EG0000 affected59 at risk EG0010 affected50 at risk EG0021 affected50 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 24.1	Systematic Assessment	EG0002 affected59 at risk EG0016 affected50 at risk EG0027 affected50 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 24.1	Systematic Assessment	EG0002 affected59 at risk EG0011 affected50 at risk EG0021 affected50 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 24.1	Systematic Assessment	EG0001 affected59 at risk EG0012 affected50 at risk EG0020 affected50 at risk EG003
Dizziness	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected59 at risk EG0011 affected50 at risk EG0024 affected50 at risk EG003
Headache	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0004 affected59 at risk EG0014 affected50 at risk EG0025 affected50 at risk EG003

ID	Term
D003920	Diabetes Mellitus
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases